title: Large normal and intermediate alleles in the context of SCA2 prenatal diagnosis.
abstract: In 2001 a program for predictive testing of Spinocerebellar Ataxia type 2 was developed in Cuba, based on the detection of an abnormal CAG trinucleotide repeat expansion in the ATXN2 gene. A descriptive study was designed to assess the implications of ATXN2 large normal and intermediate alleles in the context of the SCA2 Prenatal Diagnosis Program. Four clinical scenarios were selected based upon the behaviour of large normal and intermediate alleles when passing from one generation to the next, showing expansions, contractions, or stability in the CAG repeat size. In some populations, traditional Mendelian risk figures of 0 % or 50 % may not be applicable due to the high frequency of unstable large normal alleles. Couples with no family history of SCA2 may have a >0 % risk of having an affected offspring. Similarly, couples in which there is both an expanded and a large normal allele may have a recurrence risk >50 %. It is imperative that these issues be addressed with these couples during genetic counseling. These recurrence risks have to be carefully estimated in the presence of such alleles (particularly alleles ≥27 CAG repeats), carriers need to be aware of the potential risk for their descendants, and programs for prenatal diagnosis must be available for them.
authors.affiliation: Predictive Genetics Department, Center for the Research and Rehabilitation of Hereditary Ataxias, Reparto Edecio Pérez, Carretera Vía Habana, Holguín, Cuba, 80100, taniacruz@hotmail.ca.
authors.forename: Tania
authors.initials: T
authors.lastname: Cruz-Mariño
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Laffita-Mesa
authors.forename: Yanetza
authors.initials: Y
authors.lastname: Gonzalez-Zaldivar
authors.forename: Miguel
authors.initials: M
authors.lastname: Velazquez-Santos
authors.forename: Raul
authors.initials: R
authors.lastname: Aguilera-Rodriguez
authors.forename: Annelie
authors.initials: A
authors.lastname: Estupinan-Rodriguez
authors.forename: Yaime
authors.initials: Y
authors.lastname: Vazquez-Mojena
authors.forename: Patrick
authors.initials: P
authors.lastname: Macleod
authors.forename: Milena
authors.initials: M
authors.lastname: Paneque
authors.forename: Luis
authors.initials: L
authors.lastname: Velazquez-Perez
mesh_terms: D000483:Alleles; D000067528:Ataxins; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins